Factors influencing expression and post-translational modification of recombinant protein C.

Factors affecting the production of recombinant human protein C were investigated. When recombinant cells producing human protein C were cultured with microcarrier in two different scales, we found that (1) as cells grew to confluence, specific productivity of the protein was decreased and that (2) the efficiency of gamma-carboxylation of the generated protein C was lower in a larger culture than in a smaller culture. Higher cell density was shown to influence the specific productivity unfavorably. On the other hand, the amount of oxygen supply as demonstrated by oxygen consumption rate in the Opticell culture system correlated well with the efficiency of gamma-carboxylation, suggesting that oxygen metabolism is somehow implicated in the post-translational modification of recombinant protein C.